The purpose of this study was to examine the potential of developing a primate model of vaginal candidiasis. Mucosal candidiasis is very common in immunocompromised individuals and is caused by Candida species, especially C. albicans. C. albicans is a commensal organism of the human intestinal and reproductive tracts and thus health individuals have demonstrable Candida-specific cell-mediated and humoral immunity. Susceptibility to mucosal candidiasis is thought to involve a dysfunction in this normal protective immunity. Protective host defense mechanisms functioning at the vaginal mucosa are poorly understood and animal models are currently being used to better understand both local and systemic immunity in response to C. albicans vaginal infection. Currently, animal models of vaginal candidiasis have been restricted to rodents (mice and rats). However, rodents are not normally colonized with C. albicans or any yeast and thus do not have the demonstrable humoral and cell-mediated immunity against C. albicans that humans have. This unfortunate circumstance makes comparison to the human disease difficult. The circumvent this, we examined whether rhesus and pigtailed macaques were asymptomatically colonized with yeast, had demonstrable Candida-specific cell-mediated immunity (proliferation of peripheral blood lymphocytes in response to Candida antigen), and could acquire an experimental vaginal C. albicans infection. Results shows that indeed both pigailed and rhesus macaques were colonized vaginally with yeast and had positive peripheral blood lymphocyte responses to C. albicans antigens. Cytokines and Candida-specific antibodies were detected in vaginal lavage fluid, the cytokines showing a Th2-type profile with high levels of IL-4 and IL-10 together with lower levels of IL-2 and IFN- . Also, epithelial cells collected from vaginal lavages of both species inhibited the growth of C. albicans in vitro similar to mouse and human vaginal epithelial cells. Interestingly, the rhesus, but not pigtailed macaques were susceptible to experimental vaginitis. This was true in untreated conditions, after reduction of normal vaginal flora, and after induction of pseudoestrus (required in rodents to establish an infection). Also of interest was the reduced vaginal epithelial cell-mediated anti-Candida activity in rhesus, but not pigtailed macaques, under pseudoestrus conditions. Thus, a very interesting differential susceptibility to experimental vaginal candidiasis has been observed in two species of macaques that may be extremely useful to understand host defense